tbuckley/cabot-search huggingface dataset:
Difference in persistence between tablets and capsules.
Authors: Shehla Zaidi, Cliff Rutter, Elisea Avalos-Reyes, Dipti Shah, Kelly McAuliff, Rashmi Grover, Lucia Feczko, Chen Liu, Emily Kipping, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2023)

e18894 Background: More recently, pharmaceutical companies have developed capsule and tablet forms of their drugs to allow a choice on dosage form. As both capsules and tablets should be bioequivalent, adherence rates between members prescribed capsules and tablets should be the same. This study compares persistency between capsule and tablet forms of enzalutamide and palbociclib. Methods: This retrospective cohort study included adult Caremark members who received enzalutamide and palbociclib between 03/01/2021 and 03/01/2022 with continuous eligibility for six months prior and 12 months post-index into the study. Members were excluded if they had a &gt; 60-day gap in fill or switched from a capsule to a tablet or vice versa during the study period. Adherence was measured using the prescription-based proportion of days covered (PDC) and defined as the sum of days with medication on hand divided by the number of days between index fill and exhaust of last fill. Continuous variables were compared with the student’s t-test and Mann-U tests; categorical variables were compared with a chi-square test. Logistic regression was utilized to assess adherence differences in capsules vs. tablets; p-values &lt; 0.05 were significant. Results: 5,997 members were included in the enzalutamide cohort; there were no insurance type or region differences (all p &gt; 0.05) between members receiving capsules and tablets. There were no significant differences in mean PDC (mean (SD) 0.963 (0.080) vs. 0.964 (0.073); p = 0.521) or adherence rates (94.2% vs. 95.2%); p = 0.215) between members receiving capsules and tablets. After adjusting for the variables in the model, there was no difference in adherence rates between tablets and capsules. Members less than 65 years of age had significantly lower adherence rates (odds ratio (OR)) 0.5 (95% confidence interval (CI), 0.35-0.71) compared to those aged 65-74. 5,361 members were included in the palbociclib cohort; there were significant differences in age, gender, type of insurance and region (all p &lt; 0.05) between members receiving capsules and tablets. There were no significant differences in PDC (0.962 (0.072) vs. 0.960 (0.072); p = 0.534) or adherence rates (94.9% vs. 94.9%); p = 1.0) between members receiving capsules and tablets. Conclusions: In this study, capsule and tablet forms of enzalutamide and palbociclib had similar adherence rates when adjusting for confounders.
A matching-adjusted indirect comparison (MAIC) of the efficacy and safety of acalabrutinib (acala) versus zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic leukemia (RR CLL).
Authors: Adam Kittai, Alan Skarbnik, Miguel Miranda, Alan SM Yong, Jack Roos, Robert Hettle, Sarah Palazuelos-Munoz, Vikram Shetty, Paolo Ghia
Journal: Journal of Clinical Oncology (2023)

7540 Background: The BTKi ibrutinib is the standard of care in RR CLL and was compared in head-to-head randomized clinical trials (RCTs) with second-generation BTKis: acala in ELEVATE-RR and zanu in ALPINE. However, major differences in these RCT's populations prevents comparison of acala and zanu. Acala was also assessed in the ASCEND RCT, which had a similar population to ALPINE but a different comparator. Thus, we used unanchored MAIC to compare the efficacy and safety of acala vs zanu using individual patient data (IPD) from ASCEND and published aggregate data from ALPINE. Methods: In the unanchored MAIC, acala IPD from ASCEND were weighted to match zanu baseline data from ALPINE. This reduced between-study differences in variables that were prognostic/effect-modifying of progression-free survival (PFS) in an exploratory multivariate cox regression analysis of ASCEND. These included sex, ECOG PS, bulky disease, prior chemoimmunotherapy, del(11q), del(17p), TP53 without del(17p), IGHV status, region, age, prior lines of therapy and Rai stage. An efficacy analysis assessed investigator-assessed PFS (INV PFS) in randomized patients with baseline data (acala, n = 149; zanu, n = 327). Pseudo IPD for INV PFS for zanu were obtained from Kaplan-Meier curves. A safety analysis assessed odds ratios (ORs) of AEs in treated patients with baseline data (acala, n = 148; zanu, n = 324). To allow comparison of the incidence of AEs, an artificial data cut-off (Feb 21, 2020) was imposed for acala to match the zanu median treatment exposure (both 28.4 months). Results: After matching, the effective sample size of acala was 99 (66.6%; 65% male; median age 66 years). 12- and 24-month INV PFS are shown below. The MAIC hazard ratio (HR) for INV PFS is similar for acala vs zanu (HR 0.90, 95% CI 0.60–1.36). The risk of having grade ≥ 3 AE (OR 0.66, 95% CI 0.41–1.05), atrial fibrillation (AF; OR 1.32, 95% CI 0.56–3.08), grade ≥ 3 AF/atrial flutter (OR 0.60, 95% CI 0.12–2.89), grade ≥ 3 hemorrhage (OR 0.61, 95% CI 0.19–2.03) or an AE leading to discontinuation (OR 1.14, 95% CI 0.61–2.13) was similar with acala vs zanu. The risk of having a serious AE (OR 0.61, 95% CI 0.39–0.97), hypertension (any grade: OR 0.18, 95% CI 0.09–0.37; grade ≥ 3: OR 0.22, 95% CI 0.09–0.54), any grade hemorrhage (OR 0.54, 95% CI 0.34–0.87) or an AE leading to dose reduction (OR 0.30, 95% CI 0.14–0.67) was lower with acala vs zanu. Conclusions: Acala and zanu have a similar efficacy in patients with RR CLL, while acala has a lower risk of grade ≥ 3 hemorrhage, any grade and grade ≥ 3 hypertension and dose reduction due to AEs vs zanu. Limitations of MAIC analyses mean the results should be viewed as hypothesis-generating. [Table: see text]
Effect of intrathecal pemetrexed on survival in patients with lung adenocarcinoma with leptomeningeal metastasis: A propensity score matching analysis.
Authors: Yaping Hong, Qian Miao, Wu Zhuang, Xinlong Zheng, Zhangzhou Huang, Yiquan Xu, Gen Lin
Journal: Journal of Clinical Oncology (2023)

e21048 Background: The effect of intrathecal chemotherapy (ITC) on the survival of leptomeningeal metastasis (LM) from lung adenocarcinoma (LUAC) has not yet been clearly defined. Methods: LUAC patients with cytologically or radiographically proven LM and receiving systemic pharmacotherapy after LM diagnosed were collected at the Fujian Cancer Hospital from July 2018 to March 2022. Patients were divided into intrathecal pemetrexed (IP) or non-IP groups and then propensity matched 1:1 into two groups. Among the matched cohort, the log-rank tests and multivariable Cox proportional hazards regression models were performed to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results: A total of 165 patients with LM were included; 83 were in the IP group and 82 were in the non-IP group. After PSM, 114 patients were identified in the matched cohort. There were no statistically significant differences between IP and non-IP groups in median overall survival (13.2 months versus 10.1 months; hazard ratio 0.84, 95% CI: 0.53 - 1.33; p = 0.49). In the multivariable Cox regression analysis, only ECOG PS was confirmed as an independent prognostic factor for overall survival in the matched cohort (hazard ratio 1.83, 95% CI: 1.04 - 3.23; p = 0.037). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (14.3 months versus 1.6 months; p = 0.002), but not in patients with good ECOG PS (12.8 months versus 12.6 months; p = 0.884). Conclusions: Our results indicated that IP may not bring survival benefit to all LUAC patients with LM, but may improve survival in patients with poor ECOG PS.
Factors associated with positive margins in major salivary gland cancer: An NCDB analysis.
Authors: Darby Keirns, Beau Hsia, Kiana Verplancke, Peter T. Silberstein, Xinxin Wu
Journal: Journal of Clinical Oncology (2023)

e18093 Background: Major salivary gland cancer includes malignancies of the parotid, sublingual, and submandibular glands which represent a diverse spectrum of disease. Surgical resection is often the primary treatment. Positive tumor margins after resection have been associated with disease recurrence and worsened prognosis. This study investigates various factors and their influence on margin status. Methods: 41,705 patients with surgically treated major salivary gland cancer between 2004 and 2020 were identified in the National Cancer Database (NCDB). Factors including facility type, facility volume, surgical approach, primary site, Charlson-Deyo score, age, sex, race, Hispanic origin, income, and high school attainment were compared in patients based on margin status. Both macroscopic and microscopic positive margins were considered. Multivariate binary logistic regression analysis was performed in SPSS version 28 with a significance level of p &lt; 0.05. Results: Patients treated at an Academic/Research facility were 19% less likely to have positive margins than patients treated at a Community Cancer Program. Patients treated at facilities with case volume within the top 10% were 37% less likely to have positive margins. No significant difference was found in the margin status between different surgical approaches including open, endoscopic, and robotic. Patients with non-parotid major salivary gland cancer were 15% more likely to have positive margins than parotid cancers. Patients were more likely to have positive margins with an increasing Charlson-Deyo score and an increasing age. Female and Black patients were both 9% less likely to have positive margins than their counterparts. Other racial categories, ethnicity, income, and high school attainment did not significantly impact margin status. Conclusions: Factors associated with a lower likelihood of positive margins include treatment at an Academic/Research facility, higher volume center, parotid malignancies, lower Charlson-Deyo score, younger age, female sex, and Black race. The surgical approach and other demographic factors did not demonstrate any relationship with margin status. Identifying these associations can lead to a better understanding of prognostic factors and disparities in order to improve future care. [Table: see text]
Impact of neighborhood deprivation on disability free survival in patients with aggressive B cell non-Hodgkin lymphoma.
Authors: Madelyn Burkart, Nicholas Demetriou, Ashwin Sunderraj, Shou Ma, Jane N. Winter, Leo I. Gordon, Jonathan Moreira, Reem Karmali, Ishan Roy
Journal: Journal of Clinical Oncology (2023)

7564 Background: Advancements in treatment over the last decade have greatly improved survival in B cell non-Hodgkin’s lymphoma (NHL), yet not all patients (pts) benefit the same. Non-Hispanic Black (NHB), uninsured and lower socioeconomic status pts continue to suffer worse survival. However, the impact of neighborhood deprivation on disability has not been explored. We aimed to assess the association between neighborhood deprivation and disability free survival (DFS) in NHL pts. Methods: 258 aggressive NHL pts treated between 2005-2020 were included. Pts without documented follow up were excluded. Race/ethnicity was categorized as non-Hispanic white (NHW), Hispanic, NHB and other. Primary outcomes included progression free survival (PFS), overall survival (OS) and DFS. DFS was defined as time to needing any rehabilitative, home-health or skilled nursing services immediately following induction therapy, indicating disability and lack of functional independence. Neighborhood deprivation was assigned using the national Area Deprivation Index (ADI), a validated measure classifying neighborhood adversity. Pts were categorized into high (67-99), intermediate (34-66) or low (1-33) ADI scores, with least disadvantaged designated by lower scores. Kaplan-Meier analyses were used to compare PFS, OS and DFS. Results: Demographic data is shown in the table; 45% were female, 65% were NHW, 10% were NHB, 8% were Hispanic and 10% were other. Median age at diagnosis was 57 years. There was no difference in PFS or OS between racial/ethnic groups (p=0.91 and p=0.23 respectively). Payor source influenced both PFS and OS (p&lt;0.001 and p&lt;0.001 respectively), with self-pay associated with worse PFS and OS. Neighborhood deprivation based on ADI did not influence PFS (p=0.33) or OS (p=0.76). High ADI score was associated with worse DFS compared to lower ADI scores (p=0.03). ADI score differed significantly based on race/ethnicity (p&lt;0.0001), with more NHB pts residing in areas of high ADI scores (40% vs 5% NHW vs 10% Hispanic). There was no association between ADI score and a pt’s ECOG performance status, IPI score or albumin at diagnosis (p=0.87, p=0.78 and p=0.59 respectively). Conclusions: NHL pts with higher neighborhood adversity experience more disability after treatment despite similar survival. Further work is needed to better understand how neighborhood factors are contributing to disability before community-level strategies for improvement can be developed. [Table: see text]
Fixed-duration ibrutinib + venetoclax for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): 4-y follow-up from the FD cohort of the phase 2 CAPTIVATE study.
Authors: Paul M. Barr, John N. Allan, Tanya Siddiqi, William G. Wierda, Constantine Si Lun Tam, Carolina D. Moreno, Alessandra Tedeschi, Edith Szafer-Glusman, Cathy Zhou, Chris Abbazio, James P. Dean, Anita Szoke, Paolo Ghia
Journal: Journal of Clinical Oncology (2023)

7535 Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of first-line ibrutinib (I) + venetoclax (V) in CLL/SLL. Follow-up results from the fixed duration (FD) cohort showed 3-y PFS rate of 88% overall and rates ≥80% in patients (pts) with high-risk features (Wierda, ASCO 2022). Here we present updated results from the FD cohort with 4-y follow-up. Methods: Pts aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Responses were investigator assessed per iwCLL 2008 criteria. Undetectable minimal residual disease (uMRD; &lt;10 ‒4 ) was assessed by 8-color flow cytometry. Results: 159 pts were enrolled, including pts with high-risk features of unmutated IGHV (uIGHV) (56%) or del(17p) and/or TP53 mutation (17%). Median time on study was 50 mo (range 1‒53). At 4 y of follow-up, the best CR rate was 58% and ORR was unchanged at 96%. At 4 y, PFS rate was 79% (95% CI 71‒84) and OS rate was 98% (95% CI 94–99). 4 y PFS rates were numerically lower in pts with uIGHV (73%) or del(17p) and/or TP53 mutation (63%), while OS rates remained consistently high (Table). 4 y PFS rates by MRD status 3 mo after stopping treatment (EOT+3) were significantly higher overall in pts with uMRD vs detectable MRD (dMRD) in PB (90% vs. 66%, Table); this difference was minimal at 24 mo (100% vs 91%). Median TTNT was not reached overall (range 1–53 mo); the 4 y rate of freedom from next treatment was 84% (95% CI 77–89). Second malignancies continue to be collected off treatment; 1 AE of prostate cancer occurred during this y of follow-up. To date, 19 pts with PD after completing fixed duration I+V in either the FD cohort or MRD cohort placebo arm initiated retreatment with I. Responses in 17 pts with available data were 1 CR, 13 PR, and 1 each PR with lymphocytosis, SD, and PD. Median time on retreatment was 11 mo (range 0–39). The most common AEs (≥10%) with retreatment were diarrhea (n=3), COVID-19 (n=3), and anemia (n=2). In addition, 4 pts have started I+V retreatment to date. Conclusions: Results of the CAPTIVATE study support I+V as an all-oral, once-daily fixed-duration regimen for previously untreated pts with CLL/SLL. With 4 y follow-up, fixed-duration I+V continues to provide deep, durable remissions with clinically meaningful PFS and time off treatment, including in pts with high-risk disease features. New safety findings off-treatment were expectedly negligible, highlighting the benefits of a fixed duration regimen. Promising responses were observed upon retreatment with I in progressing pts. Clinical trial information: NCT02910583 . [Table: see text]
Anlotinib plus irinotecan or docetaxel in small-cell lung cancer (SCLC) relapsed within six months: Updated results from a single-arm, phase Ⅱ study.
Authors: Minna Zhang, Xueqin Chen, Hong Jiang, Jiaoli Wang, Jian Ye, Shenglin Ma, Bing Xia
Journal: Journal of Clinical Oncology (2023)

e20629 Background: There is still no unsatisfactory treatment strategy for patients (pts) with advanced SCLC relapsed within six months after first-line treatment, although chemotherapy alone is the standard treatment. Anlotinib, an oral multitarget tyrosine kinase inhibitor, effectively inhibits angiogenesis and enhances tumor cell response to chemotherapy. In the ALTER 1202 trial, anlotinib had significantly improved progression-free survival (PFS) and overall survival (OS) of advanced SCLC pts who received at least two lines chemotherapy. Therefore, we presented the updated efficacy and safety of anlotinib plus irinotecan or docetaxel in SCLC relapsed within six months after first-line treatment. Methods: Eligible pts with advanced SCLC who have relapsed within six months after first-line platinum-based treatment received anlotinib (12mg, QD from day 1 to 14 of a 21-day cycle, the dose could be adjusted to 10mg or 8mg according to the patient's tolerance) and irinotecan (65mg/m 2 , day1,8, q3w, up to 4 cycles) or docetaxel (60mg/m 2 , q3w, up to 4 cycles) until progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included PFS, the disease control rate (DCR), OS and safety. Results: As of Jan 31, 2023, we recruited 39 pts, among which 36 pts (median age: 63.2 years, male: 86.1%, ECOG PS 1: 80.6%, brain metastasis: 58.3%, liver metastasis: 36.1%) were eligible for efficacy analysis. Median follow-up time was 17.2 months (95% Cl, 8.27 -26.13 ). Of 36 evaluable pts, 1 pts had complete response (CR) , 20 pts reached partial response (PR) and 11 pts had stable disease(SD). The ORR was 58% (21/36) and the DCR was 89% (32/36), respectively. The median PFS was 4.4 months (95%Cl: 3.73- 5.08). The median OS was 7.9 months (95%Cl: 5.28-10.52). The Progression-free survival and overall survival in patients with recurrence &gt; 3 months and ≤ 6 months (PFS 6.5 m and OS 11.9 m) after first-line therapy improved more significantly than in patients with recurrence ≤ 3 months (PFS 4.1 m and OS 5.9 m). Most common grade 1-2 treatment-related adverse events (TRAEs) included weakness(58.3%), anorexia(38.9%), anemia(25%), hypertension (15.6%), Oral mucositis (13.9%) and leucopenia (11.1%). 3 pts (8.3%) suffered from grade 3 AEs, which were thrombocytopenia, leukopenia, and anemia. Conclusions: Anlotinib combined with irinotecan or docetaxel as second-line treatment for non-sensitive recurrent SCLC (i.e., extensive-stage disease time to relapse: 0-6 months) showed superior efficacy and safety compared with standard chemotherapy. It may become a novel therapeutic strategy for the population. Clinical trial information: NCT04757779 .
Results from two phase II studies of SI-B001, an EGFR×HER3 bispecific antibody, with/without chemotherapy in patients (pts) with recurrent and metastatic head and neck squamous cell carcinoma (HNSCC).
Authors: Liqiong Xue, Kunyu Yang, Meiyu Fang, Xuelei Ma, Wen Zou, Muran Ding, Zhaoxiang Wang, Yujia Peng, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Sebastian Olivo, Yi Zhu, Ye Guo
Journal: Journal of Clinical Oncology (2023)

6037 Background: SI-B001 is an EGFR×HER3 bispecific antibody. We present the efficacy and safety results from two ongoing studies of SI-B001, S209 and S206, in recurrent and metastatic HNSCC. Methods: S209 included pts with recurrent and metastatic HNSCC progressed on prior anti-PD-1/L1 plus platinum-based chemotherapy (PBC). Pts were treated with SI-B001 16mg/kg IV QW. S206 included pts with recurrent and metastatic HNSCC progressed on prior anti-PD-1/L1 with or without PBC and received no more than two lines of treatment. Pts enrolled in S206 were divided into two groups: Group A, pts without prior exposure to paclitaxel were treated with SI-B001 (12mg/kg IV QW) plus paclitaxel (80mg/m 2 IV QW); Group B, pts with prior exposure to paclitaxel were treated with SI-B001 (12mg/kg IV QW) plus docetaxel (35mg/m 2 IV D1D8D15 Q4W). The study endpoints of the two studies were identical. The primary endpoint was objective response rate (ORR) by investigator per RECIST v1.1. Secondary endpoints were ORR by independent central review, progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall Survival (OS), and safety. Results: As of Dec 31, 2022, 11 pts in S209 received SI-B001. Pts had a median of 4 prior lines of therapy. In 9 out of 11 pts who have at least 1 post baseline tumor assessment in S209, ORR (n/N) was 22.2% (2/9), mPFS [95%CI] was 2.7 [1.8-7.9] mo. 29 pts in S206 received SI-B001 plus chemotherapy, including 19 pts in Group A and 10 pts in Group B. In 22 pts who had at least 1 post baseline tumor assessment, ORR was 45.5% (10/22), mPFS was 5.1 [3.7-5.6] mo. 1 nasal sinus cancer pt enrolled had stable disease (SD). 14 out of the 18 pts who have at least 1 post baseline tumor assessment in Group A, ORR was 64.3% (9/14) mPFS was 5.6 [5.1-6.3] mo. 8 out of 10 pts who have at least 1 post baseline tumor assessment in Group B, ORR was 12.5% (1/8), mPFS was 1.9 [1.2-3.7] mo. The most common grade 3 and above treatment-related adverse events (TRAEs) in S209 was Hypomagnesaemia (9%). The most common grade 3+ TRAEs in S206 were rash (16%), anaemia (8%) and white blood cell count decreased (8%). No SI-B001 drug-related deaths occurred in either study. Conclusions: SI-B001 plus paclitaxel demonstrated potential improvements in ORR and DCR compared with SI-B001 monotherapy in recurrent and metastatic HNSCC. The toxicity of SI-B001 plus chemotherapy in HNSCC is manageable and tolerable. Clinical trial information: NCT05044897 ; NCT05054439 . [Table: see text]